T Donáth

Semmelweis University, Budapeŝto, Budapest, Hungary

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Publications (38)37.57 Total impact

  • Ernest Adeghate · Tibor Donath · Abdu Adem
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    ABSTRACT: The prevalence of diabetes mellitus (DM) continues to increase because of sedentary life style and inappropriate diet. DM is one of the most common metabolic diseases, affecting more than 240 million people worldwide. It is projected that the number of people with DM will continue to increase in the next decade. Alzheimer disease (AD) is the most common cause of dementia, and affects over 24 million people globally, mostly senior citizens. The worldwide prevalence of AD is estimated to double in the next 20 years. How are these two chronic and debilitating diseases similar? Do they have common denominators? AD is similar to DM in many ways, in that both are associated with defective insulin release and/or signalling, impaired glucose uptake, amyloidosis, increased oxidative stress, stimulation of the apoptotic pathway, angiopathy, abnormal lipid peroxidation, ageing (in type 2 DM), brain atrophy, increased formation of advanced glycation end products and tau phosphorylation, impaired lipid metabolism and mitochondrial pathology. The pathogenesis of both AD and DM has genetic as well as environmental components. Both can also cause impaired cognition and dementia. All of these common denominators indicate that AD and DM share a lot of factors in terms of pathophysiology, histopathology and clinical outcome. These similarities can be used in the search for and design of effective pharmacotherapy for AD, since potent therapeutic agents such as insulin, incretins, oral hypoglycaemic agents and antioxidants used in the management of DM may play a key role in the treatment of patients with AD.
    No preview · Article · Apr 2013 · Current Alzheimer research
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    ABSTRACT: The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24 h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18 h after STZ treatment. A near to complete degranulation of beta cells settled at 21 h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3 h after STZ treatment and remained high after a reduction at 6 h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1 h after STZ treatment and remained low after a reduction at 6-9 h post STZ treatment. STZ elicited significant dose-dependent increases in insulin secretion from the isolated pancreas. The early changes in catecholamine level may be used in screening and follow-up studies on diabetes mellitus.
    No preview · Article · May 2010 · Experimental and Clinical Endocrinology & Diabetes
  • K Altdorfer · G Bagaméri · T Donáth · E Fehér
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    ABSTRACT: There is functional and morphological evidence that interstitial cells of Cajal (ICC) may play a role in nitric oxide (NO) dependent signal transduction. However, little is known about the nitric oxide synthase (NOS) containing ICC during inflammation. Immunocytochemical methods were used for the ultrastructural localization of NOS1-containing ICC in the wall of the colon of rats in experimental colitis. Large numbers of NOS immunoreactive (IR) nerve terminals were found in very close vicinity to smooth muscle cells as well as to blood vessels. IR nerves were found in close relationship with the ICC. The gap between the NOS IR nerve fibers and the membrane of smooth muscle cells and of ICC was 20-250 nm. In experimental colitis the number of NOS IR nerve fibers slightly decreased, however, large numbers (24%) of the ICC became IR for NOS. In the noninflamed area and in the controls, all these cells were immunonegative for NOS. Our light- and ultrastructural study suggests that some of the ICC can also synthesize NO, at least during inflammation. Therefore the change in the number and structure of ICC could play an important role in the pathogenesis of a variety of motility disorders.
    No preview · Article · Jan 2003 · Inflammation Research
  • E Adeghate · A.S. Ponery · I Ahmed · T Donáth
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    ABSTRACT: The present study was designed to compare the morphological changes occurring in pancreatic tissue fragments transplanted into the anterior eye chamber (AEC) and the subcutaneous (SC) regions of the rat. Pancreatic tissue segments were removed from the tail end of the pancreas of neonatal rats and transplanted into the AEC and SC region of the neck of homologous rats. Five weeks after transplantation, the grafts were removed and processed for light microscopy, immunohistochemistry and radioimmunoassay. In both pancreatic tissue grafts, the acinar cells degenerated completely after transplantation. In contrast to this, insulin-, glucagon-, somatostatin- and pancreatic polypeptide-positive cells and pancreatic ducts survived equally well in both the AEC and SC grafts. The pattern and percentage distribution of insulin-, glucagon-, somatostatin- and PP-producing cells in the AEC and SC grafts was similar to that observed in normal pancreas. However, the percentage distribution of glucagon- and PP-containing cells was significantly (p < 0.03) lower in SC grafts when compared to normal. Radioimmunoassay showed that the AEC and SC pancreatic tissue grafts contained large quantities of insulin and glucagon. However, the insulin content of AEC was slightly but not significantly higher than that of SC grafts. The protein content of pancreatic tissue grafts in these transplantation sites was still significantly (p < 0.05) lower compared to normal. Lymphatic infiltration was also more conspicuous in SC grafts compared to AEC grafts. This infiltration by lymphatic cells was confined only to the endocrine portion of the graft. In conclusion, pancreatic tissue grafts survived in both the AEC and SC regions of rats but the AEC appears to be more conducive to graft survival than the SC region.
    No preview · Article · Jan 2002 · European Journal of Morphology
  • E Adeghate · P Schattner · A Péter · E Dunn · T Donáth
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    ABSTRACT: The aim of this study was to examine the disease characteristics and complications of diabetes mellitus in patients in a Hungarian rural community. Data relating to age, sex, date of onset of diabetes, fasting blood glucose values and all diseases associated with diabetics were retrieved from the medical records of patients. Almost six percent (5.7%) of the population has diabetes mellitus. The percentage of Type I diabetic patients in this population was 5.8 percent. The prevalence of diabetes was slightly but not significantly higher in females than in males. The mean age of the diabetic population was 52.1 +/- 11.3 for male and 53.47 +/- 15.7 for the female patients. The peak age of onset of diabetes mellitus was in the sixth decade of life. The mean fasting blood sugar value was 10.64 +/- 0.6 and 10.57 +/- 0.5 mmol L(-1), in male and female diabetic patients (n = 103), respectively. Diabetic patients presented with many signs and symptoms in the general practice setting. The findings of this study showed that diabetics present with many disease conditions and signs and symptoms in the general practice setting. Many of these conditions are known to be associated with diabetes while others are not. As a result of the adverse effects of diabetes mellitus on the cardiovascular system and on body metabolism as a whole, the damage and morbidity caused by diabetes mellitus may have been underestimated. The results of this study have shed light on the unrecognised complications of diabetes mellitus.
    No preview · Article · Aug 2001 · Archives of Physiology and Biochemistry
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    ABSTRACT: Vasoactive intestinal polypeptide (VIP) is an inhibitory non-adrenergic, non-cholinergic transmitter, which mediate in the relaxation of sphincters of the gastrointestinal tract. The aim of this study was to determine whether there is a change in the pattern of innervation and tissue content of VIP in the rat gastroduodenum after the onset of streptozotocin (STZ)-induced diabetes mellitus. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg Kg(-1)). Four weeks after the induction of diabetes mellitus, the rats were anaethetised and the pancreata were removed for further processing. VIP was localized and measured in normal and diabetic rat gastroduodenal tissues by immunohistochemistry and radioimmunoassay, respectively. VIP immunoreactivity was stronger in the ganglion cells of the submucosal and myenteric plexuses of the gastric antrum and duodenum of normal rats (n = 6) when compared to that of diabetic rats (n = 6). Moreover, the number of VIP-positive neurons was significantly lower in the gastrointestinal tract of diabetic rats compared to normal. The VIP content of the gastric antrum and duodenum of diabetic rat was significantly lower (p< 0.05) than that of normal rat. In contrast to the lower tissue levels of VIP in the gastroduodenal segment of diabetic rats, the plasma level of VIP was significantly higher (p< 0.04) in diabetic rat compared to normal. The plasma level of VIP in normal rats was comparable to that measured in normal human beings. A low tissue level of VIP in the gastroduodenal tract of diabetic rat may contribute in part to the abnormal gut motility observed in diabetic patients.
    No preview · Article · Jul 2001 · Archives of Physiology and Biochemistry
  • E Fehér · K Altdorfer · T Donáth · J Fehér
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    ABSTRACT: Intrinsic nitric oxide synthase (NOS)-containing nerve cells and fibers were studied in the wall of the pylorus of cat at the ultrastructural level using ABC immunocytochemistry. Large numbers of NOS immunoreactive (IR) nerve cell bodies were observed in the myenteric and in the submucous plexuses, and few in the tunica propria mucosa. The NOS IR nerve fibers were most abundant in the inner circular muscle layer and in the tunica mucosa. They were found in very close vicinity to the smooth muscle cells of the inner circular muscular layer as well as to the blood vessels and the epithelial lining. The gap between the NOS IR nerve fibers and the membrane of the target cells was 20 to 250nm. Apparent synaptic contacts were observed between the IR nerve fibers and unlabelled nerve processes and other non IR nerve cell body. It is confirmed that NO might influence smooth muscle cell activity, regulate blood flow and modulate the function of the epithelial cells. Our ultrastructural study suggested that some of the NOS containing neurons belong to the intrinsic interneurons and have a regulatory effect on other intrinsic nerve elements involved in local neuronal reflexes.
    No preview · Article · May 2001 · European Journal of Morphology
  • E Adeghate · T Donáth
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    ABSTRACT: Intrinsic nerves play a crucial role in the regulation of body functions. It is therefore of paramount importance to be able to study the biology of intrinsic nerves in tissue grafts. The anterior eye chamber of rats has long been used to study different biological mechanisms, growth and differentiation of a variety of tissues, because of the transparency of the cornea, which also allows macroscopic changes to be seen. Despite its extended use, a detailed, easy to follow description of the technique of tissue and cell transplantation into the anterior eye chamber has not been presented. In this study, pancreatic tissue fragments were transplanted into the anterior eye chamber of rats alone or with brain tissue fragments to examine the survival and viability of intrinsic nerves in these tissue fragments, which have been detached from their original extrinsic nerves. The pancreatic transplants contained intact 5-HT and AChE-positive intrinsic neurons. The brain tissue grafts contained many AChE-enzyme reactive cells. The method is simple and can be used to study the morphology or physiology of intrinsic neurons in any tissue fragment. The grafts are easily vascularised and reinnervated because of the rich blood and nerve supply of the iris which forms the bed of the anterior eye chamber. The graft will also survive with ease because the anterior eye chamber is an immunologically privileged site. In conclusion, the intrinsic nerves of pancreatic and brain tissue fragments can survive after several weeks of transplantation into the anterior eye chamber of rats. In addition to this, these intrinsic nerves have the ability to produce and or store neurotransmitters and their enzymes.
    No preview · Article · Dec 2000 · Brain Research Protocols
  • E Brazda · L Flautner · L Harsányi · T Donáth

    No preview · Article · Mar 1998 · Transplantation Proceedings
  • E Brazda · L Flautner · L Harsányi · T Donáth · E Adeghate

    No preview · Article · Mar 1998 · Transplantation Proceedings
  • E Adeghate · T Donáth
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    ABSTRACT: The administration of exogenous insulin ameliorated the symptoms and increased the life expectancy of insulin dependent diabetic patients, but could not cure or prevent the devastating complications including retinopathy, nephropathy and angiopathy. It was recognised that despite insulin therapy, the severity and frequency of the degenerative late complications are still high in patients suffering from diabetes mellitus. The recognition of the increased frequency of and complications accompanying the disease has intensified efforts by scientists to find the form of pancreatic tissue to be transplanted and the suitable site in a bid to secure an insulin producing graft. This review presents an update in pancreatic organ and fragment transplantation. The history of the pancreas is also brought into limelight to show the long, hard and exciting path pancreas and diabetes mellitus have both gone through. An account is also given of experimental and clinical pancreatic whole organ/fragment transplantation including transplantation sites, the evaluation of the viability of pancreatic grafts and the complications of transplantation. Pancreatic islet transplantation is not discussed.
    No preview · Article · Feb 1998 · Acta chirurgica Hungarica
  • Z Ember · E Fehér · T Donáth
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    ABSTRACT: To investigate the age-related alterations of pancreatic distribution of nitric oxide synthase in rats, we applied light microscopic immunocytochemistry. Tissue samples were obtained from the pancreata of 5-day-old rat newborns and 120-day-old adult rats and processed for immunocytochemistry using anti neuronal nitric oxide synthase primary serum with the avidin-biotin-streptavidin complex method. Nitric oxide synthase immunopositive intrinsic nerve cells and perivascular/periacinar nerve fibers could be seen in both the newborn and the adult rat pancreas. In addition to the labelled neuronal structures we detected some immunoreactive acinar cells in the newborns, while the neonatal ductal epithelium and the islet cells were immunonegative. Strong staining for nitric oxide synthase was observed in the adult ductal epithelial cells and moderate positivity was displayed by the adult islet cells. The localization of nitric oxide shows age-related changes mainly in the non-neuronal structures of the rat pancreas: these findings could form the morphological base of pancreatic dysfunctions in the aged.
    No preview · Article · Sep 1997 · Orvosi Hetilap
  • E Brázda · L Flautner · L Harsányi · E Adeghate · T Donáth
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    ABSTRACT: To determine an in vitro marker of viability during pancreatic preservation, 12 pigs underwent total pancreas harvesting, and graft were stored in Euro-Collins or Belzer perfusion solution for up to 24 hours. Amylase concentration of the storage solution was analyzed in regular periods and tissue samples were taken for acridine-orange histochemical evaluation of viability in the same time. In vitro pancreatic amylase release (IU/g pancreas tissue) was calculated from the volume of solution and the weight of graft. A significant increase of amylase release was found in the course of preservation in both media. Comparing amylase release in different solutions we found significant difference between Euro-Collins and Belzer media (4 hours: 6.45 IU/g vs. 2.2 IU/g, 8 hours: 11.5 vs. 3.58, 24 hours: 8.7 vs. 42.8, respectively). Comparison of amylase release with histochemical evaluation of viability showed strict correlation. We concluded that amylase release is a good marker for exocrine tissue destruction as well as viability of preserved pancreas. Our data confirms that Belzer solution is superior in pancreatic preservation. It is suggested that after adaptation into human model in vitro pancreatic amylase release could be a time- and cost-saving, useful method in predicting pancreatic transplant function prior graft implantation.
    No preview · Article · Feb 1997 · Acta chirurgica Hungarica
  • K Altdorfer · E Fehér · T Donáth · J Fehér
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    ABSTRACT: Combined nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) immunocytochemistry were used to study the distribution of NOS- and VIP-containing nerve elements in the feline pylorus. A large number of stained multipolar neurons was found in the myenteric plexus. However, some NADPH-d and NOS positive neurons were also observed in the submucous plexus and in the internal part of muscular layer. A few stained perikarya were found in the tunica mucosa, in a very close situation to the blood vessels. A large number of thin varicose fibres, with intense reaction for all markers were seen around or in close contact with the unstained perikarya to the blood vessels and some of them around the pyloric glands. The density of NOS and NADPH-d positive nerve elements was much higher than that of VIP-immunoreactive (IR) nerve elements. Our results suggest that nitric oxide (NO) might act as a regulatory neurotransmitter of the pyloric sphincter, blood flow and secretion in this region.
    No preview · Article · Aug 1996 · Neuroscience Letters
  • E Fehér · M Fodor · T Donáth
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    ABSTRACT: In order to examine the morphological substrates for neuronal connections between neuronal elements of the coeliac-mesenteric ganglion containing immunoreactivity (IR) for tyrosine hydroxylase (TH) and substance P (SP), a double-immunostaining was performed. The first antigen to SP was labelled with gold-substituted silver-intensified peroxidase, which results in a granular gold deposit of high electron and light opacity. The second antigen was the TH labelled with peroxidase and a diaminobenzidine chromogen without silver-gold particles. About of 85% of the neurons contained TH immunoreactivity in the coeliac-mesenteric ganglia. The SP IR nerve fibres were mostly found around the principal ganglion cells throughout the ganglion. In most cases they made direct synaptic contact with TH positive nerve cells and dendrites. These SP-IR boutons were also found in synaptic contact with other non-labelled postsynaptic terminals and with the soma. SP-IR nerve terminals establish both symmetrical and asymmetrical synaptic contacts with TH-IR nerve elements. Some of the nerve cells which ware TH positive, were also labelled for SP. TH positive boutons were also observed in synaptic contact with other TH-IR perikarya and dendrites. Our results suggest that SP may play an important role for the integrative activities of the ganglion with regard to gastrointestinal functions.
    No preview · Article · Feb 1996 · Acta Biologica Hungarica
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    ABSTRACT: This study demonstrates the presence and distribution of atrial natriuretic peptide (ANP) pancreastatin (PST), leucineenkephalin (Leu-ENK), galanin (GAL), and insulin in the pig pancreas. The effects of PST, ANP, Leu-ENK, and GAL on protein and amylase secretion were also investigated to determine their functional role in the control of pancreatic secretion. PST-immunoreactive cells were observed in the islet of Langerhans and in the wall of the ducts. Leu-ENK-immunopositive cells were observed in both the endo-and exocrine pancreas. It is colocalized with insulin in the islet of Langerhans. ANP immunoreactivity was discernible in nerve fibers and cells of the exocrine pancreas. GAL-immunopositive cells were observed in close association with insulin-positive cells in the islets of Langerhans and in the exocrine pancreas. Stimulation of isolated pancreatic segments with either ANP or Leu-ENK resulted in increased protein secretion and amylase output. The Leu-ENK-evoked amylase secretion was antagonized by naloxone. Pancreastatin was effective at all concentrations, but low concentration had more marked secretory effects whereas GAL failed to evoke any significant increases in either protein or amylase secretion. The results of the study have demonstrated a close association of peptidergic fibers with the secretory cells of the pancreas. The nerve fibers can release peptides that in turn can stimulate protein and amylase secretion.
    No preview · Article · Feb 1996 · Peptides
  • E Fehér · T Donáth · E Montagnese · M Fodor · J Fehér
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    ABSTRACT: Nerve elements containing neuropeptides were observed by using different antisera and Avidin-Biotin-Peroxidase technique and the distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), a marker for nitric oxide (NO) synthase were studied in the ampulla hepatopancreatica (sphincter of Oddi) in the cat. A large amount of NPY, VIP, Substance P, somatostatin immunoreactive nerve fibers were found in all layers. Some immunoreactive nerve cell bodies (NPY, VIP, SP), were also observed in the wall. The NADPH-d stained cell bodies could be distinguished according to their size and the number of processes into two neuronal subtypes: large neurons with many dendrites and smaller, round cells with one or two processes. 99% of the cell bodies showed pozitive reactions for NADPH-d. The nerve fibers with NADPH-d activity were found in all layers, chiefly in the muscle layers. According to the distribution of the nerve fibers and the relationship to the effector cells, it is suggested, that these neuropeptides might have an important role in the function, and the NO containing nerve fibers are responsible for the nonadrenergic and noncholinergic inhibitory function.
    No preview · Article · Mar 1995 · Orvosi Hetilap
  • E. Adeghate · G. Nadas · T. Donath · H. Parvez
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    ABSTRACT: The pattern of distribution of NADPH-diaphorase positive neurons in the intrinsic nerves of the gastrointestinal tract (GIT) and pancreas of the rat was investigated using enzyme histochemical technique. Different segments of the GIT and pancreas were taken from rats and processed for tile the presence of NADPH-diaphorase, an enzyme that shows the specific sites of nitric oxide. Most of the intrinsic nerves of the GIT were stained positively for NADPH. These NADPH-diaphorase positive neurons are multipolar in shape and grouped into ganglia in the submucous and muscular layers. Their processes lie parallel to the long axis of the smooth muscle fibres of the GIT. The NADPH-diaphorase-positive nerves ill the pancreas were found around the basal surfaces of pancreatic acinar tissue. It is concluded that tile GIT and pancreas have numerous NADPH-diaphorase-(NOS-) positive intrinsic nerves. These bioactive agents which regulate the production of nitric oxide may play significant roles in gastrointestinal and pancreatic function.
    No preview · Article · Jan 1995
  • E. Adeghate · T. Donath · D.J. Pallot · H.S. Parvez
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    ABSTRACT: To provide a morphological basis for understanding the role of vasoactive intestinal polypeptide (VIP) in the regulation mammalian pancreatic exocrine secretion, the present study was designed to clarify the localization and distribution of VIP in the exocrine pancreas, especially its relationship with the pancreatic acinar cells. VIP was detected in the dog pancreas using immunoelectron microscopical methods. The pancreas was found to contain VIP-immunoreactive (VIP-IR) nerve fibre terminals. These VIP-IR nerve fibre terminals have in some cases in close vicinity with the acinar cells. Some VIP-IR nerve fibres were found in the connective tissue stroma enclosed in Schwann cell processes. It is concluded that the morphological relationship of VIP nerve fibre terminals to the acinar cells is very intimate. This close association may explain why VIP is a strong bioactive stimulator of the exocrine pancreas.
    No preview · Article · Jan 1995 · Biogenic Amines
  • E Adeghate · T Donáth
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    ABSTRACT: The distribution of acetylcholinesterase (AChE) at the ultrastructural level was investigated in normal and in pancreatic fragments transplanted for 56 days into the anterior eye chamber of heterologous rats using enzyme cytochemical methods. Acetylcholinesterase reaction products were seen on the basal surface of the acinar cells in normal pancreas. Acetylcholinesterase enzyme activity was also detected on the axolemma of the surviving nerve fibres. This enzyme reaction product forms alternating thick and thin bands on the axolemma. Some of these AChE-positive nerve fibres accompany blood vessels that also survive after transplantation. AChE were seen in cytoplasm adjacent to the surviving alpha and pancreatic polypeptide cells. We conclude that the ability of some neurons and cells to produce and or store acetylcholinesterase is still retained after transplantation of pancreatic tissue into the anterior eye chamber of rats.
    No preview · Article · Mar 1994 · Cell Transplantation

Publication Stats

267 Citations
37.57 Total Impact Points


  • 1990-2013
    • Semmelweis University
      • Department of Anatomy, Histology and Embryology
      Budapeŝto, Budapest, Hungary
  • 2002
    • Emirates University
      Box Elder, South Dakota, United States
  • 1997
    • Uzsoki Hospital
      Budapeŝto, Budapest, Hungary